The dynamics of latent inhibition in rats under the action of substance P]

The role of substance P in latent inhibition was studied in experiments on rats. Administration of neuropeptide during pre-exposition of conditioned stimulus and before conditioning disturbed all signs of latent inhibition: level of reproduction, retention and resistance to amnestic action of conditioned reaction in the task of passive avoidance. Single administration of haloperidol before learning prevented the disturbance. Significance of hyperfunction of substance P in selective attention and pathogenesis of schizophrenia is discussed.     

Monoaminoxidase activity and serotonin metabolism in the brain of rats during latent inhibition]

The monoamine oxidase (MAO) activities and the concentrations of 5-HT and 5-hydroxyindoleacetic acid were investigated in four brain regions in rats during the acquisition of latent inhibition in one-trial passive avoidance task. 5-HT metabolism was not altered in the hippocampus. Changes of 5-HT metabolism were found in the frontal cortex during testing of latent inhibition and were accompanied by lowering of MAO activity. No change of 5-HT metabolism was observed in this structure at the stage of pre-exposition to conditioned stimulus. 5-HT metabolism was activated at the stage of pre-exposition to conditioned stimulus in the amygdala and striatum and was maintained on high level, in these structures during testing of latent inhibition. The data presented here indicate that serotoninergic system in various brains regions is specifically involved in the formation of different stages of latent inhibition.     

Disruption of latent inhibition in ISIAH rats with stress-sensitive arterial hypertension

Latent inhibition phenomenon is used in the study of processes of selective attention in the context reinforcing training. The purpose of this study was a comparative analysis of the ability to ignore irrelevant stimuli in hypertensive ISIAH rats and normotensive Wistar rats with different psychoemotional statuses. Latent inhibition was formed in the passive and active avoidance tasks the development of which was preceded by repeated presentation (pre-exposition) conditioned stimulus without reinforcement. In ISIAH rats, disruption of latent inhibition in both behavioural tasks was observed as compared with Wistar rats. These data suggest that the deficit of selection information in ISIAH rats is caused by congenital weakness of internal inhibition in the adaptation to anxiogenic stimuli.     

Impairment of latent inhibition in OXYS rats with hereditary syndrome of premature aging

The effect of latent inhibition has been tested in OXYS (strain selected for accelerated aging) and Wistar (control) rats at the age of 4 months using a conditioned passive avoidance reaction. The OXYS rats displayed a higher level of anxiety in the elevated plus-maze as compared to Wistar strain. The experimental procedure consisted of preexposure stage (presentation of non-reinforced environmental stimulus), conditioning (presentation of a preexposed stimulus paired with shock), and testing the effect of latent inhibition. The effect of latent inhibition was revealed only in Wistar rats, in which the latency of transition to the dark compartment of the experimental chamber was reduced. Contrastingly, in OXYS rats the conditioned performance was not inhibited. It is suggested that aging-associated factors such as the low rate of habituation to experimental situation at the preexposure stage and the high general anxiety level of OXYS rats can interfere with inhibition of the attention to irrelevant information.     

Monoaminergic mechanisms of the amygdaloid complex actualizing conditioned reflexes of different biological modality]

Microinjection of dopamine and serotonin into the dorso-medial portions of the amygdalic complex of rats increased the latent period of conditioned defense and motor food reactions, spontaneous motor activity, the number of jerks and the value of the conditioned food reflex. Noradrenaline failed to influence the recorded indices of the conditioned food-procuring reflex, but facilitated the conditioned reaction of avoidance, significantly shortening its latent time. The results obtained pointed to the specificity of the neurochemical mechanisms realizing at the level of the amygdalic complex conditioned reflexes of various biological modality in rats.     

The regulatory effect of the functional status of the cat on the perception of an external afferent stimulus]

Experiments were conducted on cats by conditioned food-procuring method. Behavioural, vegetative reactions and a set of electrophysiological characteristics were recorded. It was found that regulatory influence of an extraneous stimulus and of artificial excitation of the brain was expressed in an increase of reactivity to conditioned and unconditioned sensory stimuli and in disinhibition of effector responses. This influence was realized not only during the development of EEG activation reaction but could be preserved over a long period in conditions of the deactivated brain state. Regulatory influence of interceptive factors is characterized by a decrease of reactivity and by inhibition of effector responses. As in the case of external effects, the realization of this influence begins with a period of brain activation and is preserved for a long time in conditions of deactivated state.     

Changes in the electrical activity of the hippocampus during elaboration of an inhibitory reaction in the dog

A conditioned alimentary instrumental reflex was elaborated in three dogs with chronically implanted electrodes to a consecutive complex conditioned stimulus consisting of two equal acoustic stimuli separated by a pause. At first, the animals reacted with motor reactions during the whole action of the complex signal. Then inhibition of reaction was elaborated at first in pause and then in response to the preparatory stimulus. In the process of stabilization of inhibition, there was an increase of similarity of spectral composition of hippocampal theta-rhythm with the values obtained in the inter-signal period. Conclusion is made that the hippocampus is not a structure necessary for the elaboration of internal inhibition. The frequency of hippocampal theta-rhythm may serve as a characteristic of the property called in Pavlov's school mobility of the nervous system.     

Neurophysiological and neurotransmitter mechanisms of behavior inhibition in normal and pathological conditions

The data concerning neurophysiological and neurotransmitter mechanisms of two principal kinds of inhibition of behavior is carried out: the inborn genetically determined inhibition and that developed in the course of training. On the basis of the experiments performed by the author and the literature on general neurophysiology the conclusion is made that development of inhibition of behavior during training (i.e. internal inhibition, including "latent inhibition") is determined by the relative strengthening of inhibitory hyperpolarization processes either locally (in a conditioned stimulus analyzer) or globally in the brain cortex and other brain structures during intensification of the inhibitory state (profound inhibition of a reflex and sleep). The main neurotransmitter in development of internal inhibition is gamma-aminobutyric acid. Inhibition of behavior without preliminary training arises either during the action of superstrong stimuli, (exceeding the maximum value inhibition) or during interaction of two and more active systems. A stronger one of these two systems suppresses another one (external inhibition, dominant inhibition, "freezing", "prepulse inhibition", etc.). These kinds of inhibition develop on the background of EEG activation, which suggests participation in their realization of reticular structures and corresponding neurotransmitters (acetylcholine, noradrenalin, dopamine and serotonin). Behavior pathology causes a break of the balanced interaction between the excitation and inhibition in the central nervous system. This affects both genetically determined forms of behavior inhibition and the learned internal inhibition.     

Characteristics of the conditioned reaction of passive avoidance in rats after destruction of the terminal dopaminergic fields in the amygdaloid complex

Character of conditioned reaction of passive avoidance was analyzed in Wistar line male rats after neurochemical destruction of terminal dopaminergic fields of the amygdalar complex. 6-hydroxydopamine was bilaterally administered to the central nucleus of the amygdalar complex after preliminary treating with desmethylimipramine for selective destruction of dopaminergic terminals. Lowering of dopamine level in the amygdalar complex led to a weakening of reproduction and to prolongation of spontaneous extinction of conditioned reaction. Features of conditioned reaction are highly similar to the effect of latent inhibition connected with attention deficit. It is suggested that activity of terminal fields of the amygdalar complex is one of the mechanisms providing for attention and intensifying selection of information in learning.     

Participation of the central noradrenergic system in the mechanisms of latent inhibition

Male Wistar rats were learnt to conditioned reaction of passive avoidance 10 days after intraperitoneal administration of 50 mg/kg of specific neurotoxin DSP4. The character of conditioned reaction reproduction, duration of its conservation and its stability against amnestic processing were analyzed. It has been found that reduction of activity of noradrenergic coerulo-cortical system does not influence the conditioned reaction reproduction but inhibits its spontaneous extinction and prevents amnesia development. The obtained data are discussed in aspect of central noradrenaline participation in latent inhibition mechanisms.     

Extension of the CS past the US can facilitate conditioning of the rabbit's nictitating membrane response

Five experiments were conducted in which the onset of a tone conditioned stimulus (CS) preceded the unconditioned stimulus (US) by 500 ms. Across experiments, the offset of the CS was extended past the offset of the US by values ranging from 0 ms to 40000 ms. Extensions of the CS of 2000 ms or greater produced acquisition of a conditioned response (CR) that was as fast or faster than in the no-extension condition (0 ms). While extension of a forward tone CS after the US enhanced excitatory conditioning, insertion of another CS (light) in a purely backward relationship with the US passed only a retardation test, indicative of latent inhibition, and not a summation test needed for conditioned inhibition. The results add to the evidence that excitatory and inhibitory processes are both engaged following US offset. Alternative theories of CS processing are discussed.     

Effects of serotonin on neuronal response induced in the sensorimotor cortex by tactile and conditioned acoustic stimuli

Neuronal firing response in the sensorimotor cortex to tactile (non-conditioned) and acoustic (conditioned) stimuli was investigated in trained cats before and after iontophoretic application of serotonin and lysergide. Three functionally distinct groups of neurons were identified from the response produced by presenting tactile and acoustic stimuli. Applying serotonin was found to facilitate preliminary and residual spike response induced by tactile stimulation; it also facilitates and modulates response in many cortical neurons to conditioned stimuli. Facilitation takes the form of reduced latency of response and increased numbers of spikes in response to conditioned stimulus presentation, especially at the initial phase of response to sound and immediately after the onset of conditioned reflex motion. Additional neurons formerly unresponsive to acoustic stimuli joined in the reaction under the effects of serotonin. Changed response patterns often evolve following minor fluctuations in background activity level. It is suggested that facilitation of response following iontophoretic serotonin application in the neocortex is associated with activation of excitatory serotonin receptors (S₂). The lysergide-induced increase in background and evoked activity noted during experimentation can apparently be put down to blockade of inhibitory serotonon (S_1B) receptors.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 3, pp. 337–347, May–June, 1990.     

Latent inhibition as a function of CS intensity in taste aversion learning

An experiment is reported in which the relationship between the intensity of a preexposed stimulus and latent inhibition was investigated, using the taste aversion learning paradigm in rats. Two concentrations of a saline solution (high, 1%; and low, 0.25%) were used during preexposure and conditioning phases in a factorial design. Two control conditions without preexposure were added, one for each stimulus concentration during conditioning. The known effect of conditioned stimulus (CS) intensity during conditioning was confirmed: the more concentrated the solution used in conditioning, the higher the acquisition rate. A direct relationship was observed between the CS intensity used during preexposure and the latent inhibition effect: the more concentrated the solution during preexposure, the lower the acquisition rate of conditioning. The implications of these results for latent inhibition theories are considered.     

The conditioned avoidance reflex and intersignal movements: the correlation of the cardiac and motor components]

In five dogs correlation was studied of heart rate (HR) and motor component of conditioned avoidance reflex (CAR), elaborated by Petropavlovski? method. Stable CAR was expressed in lifting and long (not less than 5-10 sec) holding of the paw on definite height (5-10 cm) for the avoidance of painful electrocutaneous paw stimulation in response to conditioned acoustic stimulus. The level of defensive excitation, evaluated by heart rate change was maximum before the beginning of the conditioned motor reaction. Immediately after lifting and placing the paw in the zone of security a sharp decrease of defensive excitation level ("drive" reduction) took place. Intertrial motor reactions of two types were revealed. The first type imitated the conditioned motor reaction, the second one the usual phasic bending of the paw. Against the background of intertrial movement of the first, operant type a decrease of defensive motivation took similarity as it occurred against the background of CAR during the performance response.     

Neuronal activity in the nucleus basalis magnocellularis during performance of an instrumental task

Spike activity of 95 neurons in the rabbit basal forebrain forebrain magnocellular nucleus was recorded during spontaneous behavior and instrumental conditioned performance. Almost half of the neurons (48.4%) displayed a significant (p > 0.05) negative correlation between their spontaneous discharge rate and the power of the delta rhythm in the EEG of the frontal cortex; most of these cells can be classified as projection cholinergic neurons. During instrumental conditioned performance, neurons of this subgroup responded with excitation to the conditioned stimulus, whereas presumably noncholinergic nonprojection neurons responded to the conditioned stimulus with inhibition. Excitatory response of cells in the basal forebrain magnocellular nucleus was significantly more intense as compared to trials without the conditioned reaction. On the whole, our data testify that the basal forebrain magnocellular nucleus maintains the level of arousal and attention required for the instrumental conditioned performance.     

Change in the signal properties of a conditioned stimulus during two-way avoidance conditioning in rats

Acquisition of two components of conditioned active avoidance behavior by rats was studied. First presentations of electroshock evoked a number of different behavioral reactions. However, after five trials many rats learned to escape punishment running away to another part of a shuttle-box. The efficiency of the avoidance reaction conditioning significantly depended on the ability of an animal to learn the correct escape reaction to the unconditioned stimulus. However, some animals were incapable for acquisition of the conditioned reaction despite their high level of successful escapes. Increase in the number of negative reactions to the conditioned stimulus (light) at the next stage of learning suggests that the conditioned stimulus becomes the signal of forthcoming punishment. The ability of an animal to identify the conditioned stimulus as a signal significantly affected the efficiency of conditioned avoidance acquisition.     

Neuronal activity of the cerebral cortex in cats with conditioned inhibition

Unit activity of the somatosensory cortex was studied in chronic experiments on cats during alimentary instrumental conditioned reflex performance and elaboration of conditioned inhibition (CI). First presentations of the CI signal at the beginning of CI formation caused, due to orienting reaction to a new stimulus, a levelling of the response of the neurones to the positive conditioned signal included into the CI complex. At the stage of consolidated CI, this depression proceeded gradually during the development of conditioned inhibition caused by consecutive presentations of the nonreinforced CI combination. Two groups of neurones were involved in the process of the CI performance: one of them being the same which was activated also in response to positive stimulation during performance of the conditioned response, and the second one being areactive to the positive conditioned stimulus but reducing the frequency of the background activity.     

Developmental caspase-3 activation in the rat hippocampus is involved in the maturation of instrumental behavior

Previously the developmental switch to caspase-3 activation in the rat hippocampus has been shown during the third week of life. The goal of this study was to explore effects of caspase-3 inhibition during this period on learning in a two-way avoidance paradigm. On postnatal day 18, the pups were intracerebroventricularly administered with caspase-3 inhibitor Z-DEVD-FMK. Control groups were injected with either the control peptide Z-FA-FMK or saline. Caspase-3 inhibition, naturally activated in this critical period, was found to disturb the maturation of instrumental behavior. In particular, the young adult rats of Z-DEVD-FMK group displayed less effective elaboration of escape and active avoidance reactions in two-way avoidance paradigm, accompanied with a decrease in inter-trial crossings. However, associative components of the learning did not change after caspase-3 inhibition. Conditioned emotional behavior was, in general, similar in all groups, and the number of responses related to conditioned stimulus exploration did not differ in Z-DEVD-FMK and Z-FA-FMK groups. In spite of the deficit in active avoidance conditioning in Z-DEVD-FMK group, a significant increase in incomplete or preparatory reactions to conditioned stimulus was demonstrated suggesting that the association between predictive conditioned stimulus and possibility of crossing can be elaborated. The change of exploratory behavior is unlikely to be specific for caspase-3 inhibition, being similar in Z-DEVD-FMK and Z-FA-FMK groups.     

Effects of context novelty vs. familiarity on latent inhibition with a conditioned taste aversion procedure

The latent inhibition phenomenon is observed when a conditioned stimulus is preexposed without any consequence before conditioning. The result of this manipulation is a reduction in conditioned response intensity to such a stimulus. In this study, we analyse the role of context novelty/familiarity on LI modulation by changing the context using a three-stage conditioned taste aversion procedure. Experiment 1 revealed that, similar to other learning procedures, a context change between preexposure and conditioning/testing (but not between preexposure/conditioning and testing) resulted in LI attenuation when the experimental contexts were novel. Experiment 2, using animals’ home cages as one of the contexts, revealed a different pattern of results, with an unexpected increase in LI magnitude when the context change was introduced between conditioning and test stages. The Schmajuk et al. (1996) computational model explains these results in terms of the increased novelty of the conditioned stimulus during preexposure, conditioning, and testing.     

Functional differentiation of the theta-rhythm of the hippocampus in the cat

On the model of discriminating alimentary conditioned reflex with spatial separation of the sources of conditioned (CR, light flashes) and unconditioned (feeding trough) stimuli the theta-rhythm of the dorsal hippocampus was evaluated in cats. Two types of the theta-rhythm were observed in the spectrum of the hippocampal electrical activity: low-amplitude, consisting of a slow growing theta-waves (type I) and high-amplitude consisting of rapidly increasing theta-waves (type II). The type I theta-rhythm is sensitive to noradrenaline and correlates with behavioural forms directed immediately to the realization of alimentary motivation, while the type II is sensitive to serotonin and correlates with behavioural forms directed to the source of the conditioned stimulus. Enhancement of the type II theta-rhythm takes place during a delay of the expected conditioned stimulus. It is suggested that type I theta-rhythm reflects a level of activity of the brain structures connected with unconditioned mechanisms, with realization of biological motivations, while type II theta-rhythm is connected with conditioned reinforcing stimuli; it correlates with various forms of conditioned orienting reflexes and reflects the work of the "nervous model of reinforcing stimulus".